1-181483501-CT-C

Position:

• chr1-181483501-CT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000367570.6(CACNA1E):​c.-230del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0914 in 208,618 control chromosomes in the GnomAD database, including 123 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.033 (112 hom., cov: 29)
  • Exomes 𝑓: 0.21 (11 hom.)
• Consequence: CACNA1E ENST00000367570.6 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.166

Genes affected

CACNA1E (HGNC:1392): (calcium voltage-gated channel subunit alpha1 E) Voltage-dependent calcium channels are multisubunit complexes consisting of alpha-1, alpha-2, beta, and delta subunits in a 1:1:1:1 ratio. These channels mediate the entry of calcium ions into excitable cells, and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. This gene encodes the alpha-1E subunit of the R-type calcium channels, which belong to the 'high-voltage activated' group that maybe involved in the modulation of firing patterns of neurons important for information processing. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Apr 2011]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-181483501-CT-C is Benign according to our data. Variant chr1-181483501-CT-C is described in ClinVar as [Likely_benign]. Clinvar id is 1320658.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1E	NM_001205293.3			upstream_gene_variant		ENST00000367573.7	NP_001192222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA1E	ENST00000367570.6	c.-230del		5_prime_UTR_variant	1/47	1		ENSP00000356542	P4
CACNA1E	ENST00000533229.1	n.205del		non_coding_transcript_exon_variant	1/7	1
CACNA1E	ENST00000524607.6	c.435-229del		intron_variant		5		ENSP00000432038
CACNA1E	ENST00000367573.7			upstream_gene_variant		1	NM_001205293.3	ENSP00000356545	A2

Frequencies

GnomAD3 genomes AF: 0.0326 AC: 4528 AN: 139036 Hom.: 112 Cov.: 29

Gnomad AFR AF: 0.0218

Gnomad AMI AF: 0.00114

Gnomad AMR AF: 0.0597

Gnomad ASJ AF: 0.0218

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.0588

Gnomad FIN AF: 0.0268

Gnomad MID AF: 0.0235

Gnomad NFE AF: 0.0256

Gnomad OTH AF: 0.0338

GnomAD4 exome AF: 0.209 AC: 14541 AN: 69550 Hom.: 11 Cov.: 0 AF XY: 0.210 AC XY: 7595 AN XY: 36138

Gnomad4 AFR exome AF: 0.140

Gnomad4 AMR exome AF: 0.215

Gnomad4 ASJ exome AF: 0.222

Gnomad4 EAS exome AF: 0.263

Gnomad4 SAS exome AF: 0.131

Gnomad4 FIN exome AF: 0.191

Gnomad4 NFE exome AF: 0.208

Gnomad4 OTH exome AF: 0.205

GnomAD4 genome AF: 0.0326 AC: 4536 AN: 139068 Hom.: 112 Cov.: 29 AF XY: 0.0337 AC XY: 2271 AN XY: 67370

Gnomad4 AFR AF: 0.0219

Gnomad4 AMR AF: 0.0598

Gnomad4 ASJ AF: 0.0218

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.0590

Gnomad4 FIN AF: 0.0268

Gnomad4 NFE AF: 0.0256

Gnomad4 OTH AF: 0.0336

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs111237511; hg19: chr1-181452637;